Abstract Prostate cancer (CaP) is the most common non-skin cancer in men and third most common cause of cancer deaths in men. Black men experience a higher burden of incidence and mortality from CaP compared to White men. The Prostate-Specific Antigen (PSA) test, a commonly used biomarker for early diagnosis and management of CaP, cannot alone accurately predict the presence of CaP, its aggressiveness, or the risk of post-treatment recurrence. The widespread use of PSA testing in CaP screening is controversial partially because patients with benign enlargement of the prostate often have elevated levels of PSA and many men with diagnosed CaP have a normal PSA. Consequently, a search for more effective prostate tumor biomarkers is overdue. KAPS Biotech?s preliminary studies show that concurrent measurements of the levels of serum cytokines such as IL-8, TNF-?, and sTNF-R1 (KAPS biomarker) provide a significant advantage as a CaP biomarker over PSA measurements alone in differentiating men with CaP from men without CaP. However, these preliminary studies were carried out on a small sample and essentially contained no Black men. The central hypothesis of this proposal is that both Black and White men with CaP have altered circulating levels of KAPS biomarker compared to men without CaP. Further, the extent to which these levels are altered will vary according to CaP risk factors and can be used as a tool to improve the early detection of CaP and CaP treatment decision-making. Due to the reported significant racial differences in the diagnoses of and mortality from CaP, future CaP biomarker studies should include a racially diverse sample of men, especially Black men. Therefore, newly developed biomarkers must be validated in a robust and racially diverse population of men to improve the specificity of CaP diagnosis and to better inform CaP treatment decision making. To test the central hypothesis, this Fast Track proposal proposes the following specific aims: Phase I: A small, one-year prospective proof-of-principle study to determine whether KAPS biomarker (concurrent measurements of IL-8, TNF-?, and sTNFR1) can distinguish those with CaP from those without CaP among Black and White men. Phase II: A large, prospective cohort study to address the following aims: 1. Determine whether KAPS biomarker can prospectively distinguish those with CaP from those without CaP among a large sample of Black and White men. 2. Determine whether KAPS biomarker can prospectively distinguish men with high-risk CaP from those with indolent CaP among a large sample of Black and White men with CaP.